Nie Weihong, Cao Wenxuan, Zhuang Yingzhu, Yang Sumin, Zhang Hui, Hu Haoyu, Shi Chunying, Zhang Hong
Department of Cardiovascular Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China; Medical College, Qingdao University, Qingdao, Shandong Province, China.
Department of Morphology, Qingdao Huanghai University, Qingdao, Shandong Province, China.
Heart Lung Circ. 2025 Jul;34(7):704-718. doi: 10.1016/j.hlc.2025.03.012. Epub 2025 Jun 10.
Vascular smooth muscle cell (VSMC) proliferation and migration contribute to vascular remodelling in thoracic aortic aneurysms (TAA). An increase in cytosolic Ca concentration triggers VSMC proliferation and migration. Piezo1, a mechanosensitive cation channel, may be involved in the proliferation and migration of VSMCs, and potentially in the development of TAA.
This study analysed Piezo1 and its potential downstream protein extracellular signal-regulated kinases (ERK) in aortic surgical specimens from six patients with TAA and six controls. In in vitro experiments, Yoda1, a Piezo1 agonist, SCH772984, an ERK inhibitor, si-Piezo1, used for silencing the piezo1 gene, and LM22B-10, an ERK activator, were used to regulate the expression of Piezo1 and ERK in rat thoracic aortic VSMCs. The effects of these treatments on cell proliferation, migration, apoptosis, and phenotypic switch were measured.
Through the comparison of human samples, it was discovered that the expressions of Piezo1 and ERK in the aortic media of TAA were higher than in normal samples. Additionally, the levels of VSMC proliferation and apoptosis were higher in TAA samples. This confirmed that upregulation of Piezo1 can induce cell proliferation and migration by activating the ERK pathway. It was also found that Piezo1/ERK signalling does not affect cell apoptosis. Additionally, it was discovered that inhibiting Piezo1/ERK signalling can induce a phenotypical switch in cells.
These data indicate that Piezo1 is significantly activated in aortic VSMCs from patients with TAA, which may be involved in TAA by promoting VSMC proliferation and migration through the ERK signalling pathway. This study provides a new insight into the biological action of the Piezo1/ERK signalling pathway in the pathogenesis of TAA.
血管平滑肌细胞（VSMC）的增殖和迁移有助于胸主动脉瘤（TAA）的血管重塑。细胞溶质钙浓度的增加会触发VSMC的增殖和迁移。Piezo1是一种机械敏感阳离子通道，可能参与VSMC的增殖和迁移，并可能与TAA的发生发展有关。
本研究分析了6例TAA患者和6例对照者的主动脉手术标本中的Piezo1及其潜在的下游蛋白细胞外信号调节激酶（ERK）。在体外实验中，使用Piezo1激动剂Yoda1、ERK抑制剂SCH772984、用于沉默Piezo1基因的si-Piezo1以及ERK激活剂LM22B-10来调节大鼠胸主动脉VSMC中Piezo1和ERK的表达。测量这些处理对细胞增殖、迁移、凋亡和表型转换的影响。
通过对人体样本的比较，发现TAA主动脉中膜中Piezo1和ERK的表达高于正常样本。此外，TAA样本中VSMC的增殖和凋亡水平更高。这证实了Piezo1的上调可通过激活ERK途径诱导细胞增殖和迁移。还发现Piezo1/ERK信号通路不影响细胞凋亡。此外，发现抑制Piezo1/ERK信号通路可诱导细胞发生表型转换。
这些数据表明，Piezo1在TAA患者的主动脉VSMC中被显著激活，可能通过ERK信号通路促进VSMC增殖和迁移而参与TAA的发生。本研究为Piezo1/ERK信号通路在TAA发病机制中的生物学作用提供了新的见解。
